External Validity: Poor. Studies on populations in high-risk areas may not be applicable to low-risk areas such as the United States.

Harms

Based on solid evidence, screening would result in uncommon but serious side effects associated with endoscopy, which may include perforation, cardiopulmonary events, aspiration pneumonia, and bleeding requiring hospitalization.

False-positive tests are also common in association with serum pepsinogen or gastric photofluorography.

References

Description of the Evidence

Background

Incidence and mortality

In 2015, it is estimated that 24,590 Americans will be diagnosed with
gastric cancer and 10,720 will die of it.[1] Two-thirds of people diagnosed with gastric cancer are older than 66 years. The disease is much more common
in other countries, principally Japan, Central Europe, Scandinavia, Hong Kong,
South and Central America, the Soviet Union, China, and Korea. Gastric cancer is
a major cause of death worldwide, especially in developing countries.[2]

The
major type of gastric cancer is adenocarcinoma (95%). The remaining malignant tumors
include lymphomas, sarcomas, carcinoid tumors and other rare types. Distinguishing the common adenocarcinoma from the uncommon lymphoma may sometimes be difficult but is important, due to major differences in staging, treatment, and prognosis.[3] Gastric adenocarcinomas
can be further categorized into an intestinal type and a diffuse type.[4]
Intestinal-type lesions are frequently ulcerative and occur in the distal
stomach more often than the diffuse type. Diffuse-type lesions are associated with a
worse prognosis than the intestinal type. The intestinal type tends to
be predominant in geographic regions with a high incidence of gastric carcinoma.
The decline in the incidence of gastric cancer worldwide is largely due to a
decrease in the number of intestinal-type lesions.

Risk Factors

The incidence of gastric cancer in the United States has decreased fourfold since
1930 to approximately seven cases per 100,000 people.[5] The reasons for this
striking decrease in incidence are not fully understood but are suspected to be related to
improved storage of food and changes in diet, such as decreased salt intake. Some populations of Americans are at elevated risk, including elderly patients with atrophic gastritis or pernicious anemia, patients with sporadic gastric adenomas,[6] familial adenomatous polyposis,[7] or hereditary nonpolyposis colon cancer,[8] and immigrant ethnic populations from countries with high rates of gastric carcinoma.[9,10]

Risk factors for gastric cancer include the presence of precursor conditions
such as chronic atrophic gastritis and intestinal metaplasia, pernicious
anemia, and gastric adenomatous polyps. Genetic and environmental factors
include a family history of gastric cancer; low consumption of fruits and
vegetables; consumption of salted, smoked, or poorly preserved foods; and
cigarette smoking.[11,12] There is consistent evidence that Helicobacter pylori
infection of the stomach is strongly associated with both the initiation and promotion
of carcinoma of the gastric body and antrum, and of gastric lymphoma.[13-15] The International Agency for Research on Cancer (IARC) classifies H. pylori infection as a cause of noncardia gastric carcinoma and low-grade B-cell mucosa-associated lymphatic tissue gastric lymphoma (i.e., a Group 1 human carcinogen).[16,17] Compared with the general population,
people with duodenal ulcer disease may have a lower risk of gastric cancer.[18]

Evidence of Benefit Associated With Screening

Several screening techniques, including barium-meal photofluorography, gastric endoscopy, and serum pepsinogen have been proposed as screening methods for the early detection of gastric cancer. No randomized trials evaluating the impact of screening on mortality from gastric cancer have been reported.[12,19] Even in very high-risk areas, the positive predictive value (PPV) of the screening tests may be very low. In a screening program of 17,647 men aged 40 to 60 years in Wakayama City, Japan, the PPV of combined serum pepsinogen and barium meal with digital radiography over the 7-year period was 0.85%.[20] The positive test rates were 19.5% for serum pepsinogen and 22.5% for radiography, with a cancer detection rate of 0.28%. Over the 7-year period, there was no reduction in gastric cancer mortality compared with an age-matched surrounding population.

Barium-meal gastric photofluorography

A national program of population-based screening for gastric cancer using barium-meal photofluorography has been ongoing since the 1960s in Japan. Participation rates have been in the range of only 10% to 20%.[12,20] Although there has been a coincident decrease in mortality from gastric cancer in Japan, mortality rates have been decreasing in many developed countries despite the lack of screening programs. Case-control studies from Japan show decreases in gastric mortality in people who have undergone screening, but results from prospective studies were not consistent.[12,19]

A pilot study of community-based photofluorography was conducted in Costa Rica using the same techniques as those used in Japan’s national program (with consultation from Japanese experts).[21] People were invited by letter from a population registry to attend two rounds of screening, and a total of 6,200 eligible screened participants (of a planned 12,000) were analyzed. Their gastric cancer mortality from 2 to 7 years after screening was compared with four control groups that had not been invited to be screened, and the relative risk was about 0.5 (no p-value reported). The study was, however, prone to strong biases, including selection bias, and likely differential exclusion of people with previously diagnosed gastric cancer favoring the screened population. In addition, unlike the community controls, patients diagnosed with gastric cancer through the screening program were treated at a single referral center. The PPV of a suspicious fluorograph was 3%; the specificity in the two rounds was 67% and 80%; and the positivity rates were 34% and 20%. Despite the authors’ belief that their results provided substantial evidence that routine screening would decrease gastric cancer mortality, they concluded that the costs of screening with photofluorography would be far too high in their country.

A screening study was begun in Venezuela in 1980, using radiographic fluorography.[22] The efficacy of this program in reducing mortality from stomach cancer was evaluated by means of a case-control study, and there was no detectable reduction in mortality from gastric cancer.

Gastric endoscopy

Endoscopy appears to be more sensitive than photofluorography for the detection of gastric cancer.[23] Time-trend analysis and case-control studies of gastric endoscopy suggest a twofold decrease in gastric cancer mortality in screened versus unscreened individuals;[24-28] however, this stands in contrast to studies of stronger design.

A cohort study of endoscopic screening was conducted in Linqu County, China, where gastric cancer rates are high, in which 4,394 adult residents aged 35 to 64 years were screened. Individuals were screened at an average of 4.5-year intervals, except for a high-risk subset (689 individuals) that was screened 2 years after the initial examination. Of the 85 cases of gastric cancer occurring in the cohort, 58 were detected with screening. No impact on gastric cancer mortality was observed among screened individuals. The standardized mortality ratio (SMR) for gastric cancer 10 years after the initial screen was 1.01 (95% confidence interval, 0.72–1.37). The SMR for all-cause mortality was significantly lower among participants because individuals with hypertension, liver disease, and chronic obstructive pulmonary disease were not eligible to participate.[29] The data were observational, and not primarily collected to evaluate the effect of screening on gastric cancer mortality. In addition, the intervals between screens may have been too long.

Serum pepsinogen

There are no studies evaluating the effect of screening with serum pepsinogen on gastric cancer mortality, and there are important limitations to its use as a screening test. Low serum pepsinogen levels indicate the presence of atrophic gastritis and are therefore applicable to the detection of presumed precursors for intestinal type gastric cancer rather than the diffuse type.[20] In addition, there are no standard cut-off values of abnormality.[12,30] Finally, eradication of H. pylori and use of proton pump inhibitors for the management of indigestion change pepsinogen levels, making interpretation of results difficult in the setting of widespread use of these interventions.[12,20]

In Japan, measurement of serum pepsinogen levels I and II (PGI and PGII) in 5,113 subjects also screened by endoscopy (13 gastric cancers detected), used cut-off points for identifying risk for gastric cancer of less than 70 ng/mL for PGI and less than 3 ng/mL for the PGI:PGII ratio. This combination provided a sensitivity of 84.6%, a specificity of 73.5%, a PPV of 0.81%, and a negative predictive value of 99.6%.[31]

Clinical considerations for high risk groups

There may be justification for screening some populations of Americans at
higher risk, although there is considerable discussion about how much incidence
would make the examination worthwhile. Potential subgroups might include
elderly patients with atrophic gastritis or pernicious anemia, patients with partial
gastrectomy,[32] patients with the diagnosis of sporadic adenomas,[6]
familial adenomatous polyposis,[7] or hereditary nonpolyposis colon cancer,[8] and immigrant ethnic populations from countries with high
rates of gastric carcinoma.[9,10]

Evidence of Harm Associated With Screening

Harms of routine screening for gastric cancer are poorly quantitated or reported, and derive chiefly from screening experiences in very high-risk areas such as Japan.[19] The most frequent harm is the occurrence of false-positive tests.[20] Exposure to the low doses of radiation (about 0.6 mSv in photofluorography) carries a theoretical but poorly quantified risk of carcinogenesis. Additional rare complications of screening may include adverse effects of premedication (used for endoscopy and sometimes photofluorography), and bleeding or perforation from endoscopy.[19] As with any screening test, there is a possibility of overdiagnosis with attendant overtreatment. Since harms such as perforation and bleeding may vary with the experience of the screening center, they may be higher in populations at low risk for gastric cancer, such as the United States, than in mass screening programs in Japan.

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Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about stomach (gastric) cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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